Department of Medicine, Centre for Gastroenterology, University of Szeged, Szeged, Hungary.
UMR 1331, Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse III, ENVT, Toulouse, France.
United European Gastroenterol J. 2024 Oct;12(8):1102-1113. doi: 10.1002/ueg2.12625. Epub 2024 Aug 6.
Gelsectan is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions.
Animals: Wistar rats received gavage with XOS, XG + PPGS or XG + PPGS + XOS, as a single dose or for 7 days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12 weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively.
Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG + PPGS + XOS failed to reverse PRS, but 7 days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D.
Gelsectan prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan can be considered as an effective therapy for IBS-D symptoms.
Gelsectan 是木葡聚糖（XG）、豌豆蛋白、葡萄籽提取物（PPGS）和木寡糖（XOS）的制剂。我们的目的是在动物模型中研究 Gelsectan 对直肠敏感性的影响、肠易激综合征伴腹泻（IBS-D）患者的腹痛以及这两种情况下的肠道通透性。
动物：Wistar 大鼠单次灌胃 XOS、XG+PPGS 或 XG+PPGS+XOS，或连续 7 天灌胃 XG+PPGS+XOS 后进行部分束缚应激（PRS）。评估直肠扩张的内脏运动反应和 Cr-EDTA 的全肠道旁细胞通透性。人类：纳入 IBS-D 和对照患者。IBS-D 患者在初始结肠镜检查和活检取样后给予 Gelsectan®治疗 12 周。记录粪便计数和疼痛评分。治疗后，再次进行结肠镜检查。在 Ussing 室中测量活检样本的通透性。通过组织学/免疫组织化学评估粘附的粘液层、Muc-2 表达以及 TNFα、干扰素 IFNγ。
动物研究：在对照大鼠中，PRS 显著增加了内脏运动反应和肠道旁细胞通透性。XG+PPGS+XOS 的单次给药未能逆转 PRS，但连续 7 天的口服治疗逆转了 PRS 诱导的直肠高敏和肠道高通透性。人类研究：Gelsectan 治疗显著减少了腹痛。与对照组相比，IBS-D 患者的肠道通透性升高，Gelsectan 恢复了升结肠的通透性。与对照组相比，IBS-D 患者的周期性酸-Schiff 染色粘液层明显变薄，在两个节段，粘液厚度和 Muc-2 阳性细胞的比例均不受 Gelsectan 治疗的影响。乙状结肠中的 IFNγ 组织水平显示 IBS-D 有适度的粘膜炎症。
Gelsectan 分别预防了大鼠的直肠高敏、人类的腹痛和大鼠和人类研究的肠道高通透性。这些作用涉及肠道通透性的恢复。基于这项转化研究，Gelsectan 可被视为 IBS-D 症状的有效治疗方法。
